Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, China.
Neuboron Medtech Ltd., Nanjing, China.
Nucl Med Biol. 2021 Mar-Apr;94-95:32-37. doi: 10.1016/j.nucmedbio.2020.12.006. Epub 2021 Jan 8.
L-isomer of 4-borono-2-F-fluoro-phenylalanine (L-[F]FBPA) was generally applied in clinic for boron neutron capture therapy (BNCT). With radiotracer validation, D-isomer of [F]FBPA (D-[F]FBPA) was found a higher tumor to normal brain tissue ratio (TBR) than its L-isomer on positron emission tomography (PET) in rat brain glioma. The present study was conducted as a first-in-human study to explore the biodistribution and radiation dosimetry of D-[F]FBPA in healthy human volunteers, compared with L-[F]FBPA.
D-[F]FBPA or L-[F]FBPA was injected intravenously. Five whole-body PET scans were performed for each subject in the next 2 h. Organ time-activity curves were drawn by measuring SUV in volumes of interest. Absorbed dose coefficient of target organs and effective dose (ED) were estimated on OLINDA/EXM.
Two healthy volunteers (both males) and three healthy volunteers (2 males, 1 female) were intravenously injected with D-[F]FBPA (5.5-7.2 MBq/kg) and L-[F]FBPA (3.9-6.8 MBq/kg) respectively. Only limited accumulation of D-[F]FBPA was observed in healthy human brain, pancreas, liver, spleen and skeleton. The ED was calculated to be 0.026 mSv/MBq. Urinary bladder wall received the highest dose of 0.28 mGy/MBq, followed by kidneys (0.06 mGy/MBq), and all the other organs received less than 0.03 mGy/MBq. For L-[F]FBPA, higher uptake in brain, pancreas, liver, spleen and skeleton could be visualized, compared with D-[F]FBPA. The ED of L-[F]FBPA was 0.020 ± 0.001 mSv/MBq. Urinary bladder wall and kidneys still received the highest dose among organs but with lower values than those of D-[F]FBPA.
D-[F]FBPA had lower activity in normal brain, liver, spleen, pancreas and skeleton, compared with its L-isomer. D-[F]FBPA is safe from a radiological standpoint.
D-[F]FBPA was safe from a radiological standpoint, and had lower activity in normal brain, liver, spleen, pancreas and skeleton than its L-isomer. This study ensures the safety and validity of D-[F]FBPA for further clinical trials in patients with cancer.
4-硼-2-F-氟苯丙氨酸（L-[F]FBPA）的 L-对映体通常用于硼中子俘获疗法（BNCT）的临床应用。通过放射性示踪剂验证，在大鼠脑胶质瘤中，D-[F]FBPA（D-[F]FBPA）的 D-对映体在正电子发射断层扫描（PET）上比其 L-对映体具有更高的肿瘤与正常脑组织比（TBR）。本研究首次在人体中进行，旨在探索 D-[F]FBPA 在健康志愿者中的生物分布和辐射剂量学，与 L-[F]FBPA 进行比较。
D-[F]FBPA 或 L-[F]FBPA 经静脉注射。每位受试者在接下来的 2 小时内进行 5 次全身 PET 扫描。通过测量感兴趣区域的 SUV 绘制器官时间-活性曲线。通过 OLINDA/EXM 估算目标器官的吸收剂量系数和有效剂量（ED）。
两名健康志愿者（均为男性）和三名健康志愿者（2 名男性，1 名女性）分别静脉注射 D-[F]FBPA（5.5-7.2MBq/kg）和 L-[F]FBPA（3.9-6.8MBq/kg）。仅在健康人的大脑、胰腺、肝脏、脾脏和骨骼中观察到有限的 D-[F]FBPA 积累。计算出的 ED 为 0.026mSv/MBq。膀胱壁接受的剂量最高，为 0.28mGy/MBq，其次是肾脏（0.06mGy/MBq），而所有其他器官接受的剂量均低于 0.03mGy/MBq。与 D-[F]FBPA 相比，L-[F]FBPA 可在大脑、胰腺、肝脏、脾脏和骨骼中观察到更高的摄取。L-[F]FBPA 的 ED 为 0.020±0.001mSv/MBq。膀胱壁和肾脏仍然是器官中接受剂量最高的部位，但低于 D-[F]FBPA。
与 L-对映体相比，D-[F]FBPA 在正常大脑、肝脏、脾脏、胰腺和骨骼中的活性较低。从放射学角度来看，D-[F]FBPA 是安全的。
从放射学角度来看，D-[F]FBPA 是安全的，其在正常大脑、肝脏、脾脏、胰腺和骨骼中的活性低于 L-对映体。本研究为 D-[F]FBPA 在癌症患者的进一步临床试验提供了安全性和有效性的保证。
